This program seeks to advance the field of Cartilage Tissue Engineering by defining strategies and principles for selecting and optimizing available sources of chondrogenic connective tissue progenitors (CTP- Cs). It will also provide the tissue engineering community with a rigorous and standardized quantitative methodology for objective evaluation and comparison of cell sourcing and processing options. Successful repair or regeneration of cartilage tissue requires a source of CTP-Cs, i.e. native cells that are capable of chondrogenic differentiation. Cartilage repair strategies must rely on one of several cell sourcing strategies. CTPs with chondrogenic potential reside in cartilage, as well as bone marrow, periosteum, muscle, fat and other tissues. Several of these tissue sources have already been or are being exploited to provide cells for cartilage repair and regeneration procedures. Although articular cartilage tissue shows little intrinsic capacity to repair, some cells in both normal and diseased cartilage tissue can be induced to proliferate and differentiate to express a chondrocytic phenotype in vitro. Such cartilage-derived CTP-Cs have become central to several treatment strategies based on transplantation of freshly isolated cartilage tissue or culture-expanded cells into a cartilage defect. To date, cell sourcing decisions and cell processing or fabrication strategies have generally not been based on quantitative assays of the concentration, prevalence or biological potential of the available cell sources. This program addresses three opportunities to improve clinical practices: 1) Define the concentration, prevalence and biological potential of chondrogenic connective tissue progenitors (CTP-Cs) in and around the adult human knee (articular cartilage, fat pad, synovium, periosteum, subchondral bone and marrow). 2) Define the relationship between cartilage tissue health and the concentration, prevalence and biological potential of CTP- Cs in human cartilage. 3) Test the hypothesis that differences in in vitro performance between CTP-C sources predict differences in in vivo performance.